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Open Access Green as soon as Postprint is submitted to ZB.
Immunostimulatory RNA oligonucleotides induce an effective antitumoral NK cell response through the TLR7.
J. Immunol. 183, 6078-6086 (2009)
RNA oligonucleotides containing immune-activating sequences promote the development of cytotoxic T cell and B cell responses to Ag. In this study, we show for the first time that immunostimulatory RNA oligonucleotides induce a NK cell response that prevents growth of NK-sensitive tumors. Treatment of mice with immunostimulatory RNA oligonucleotides activates NK cells in a sequence-dependent manner, leading to enhanced IFN-gamma production and increased cytotoxicity. Use of gene-deficient mice showed that NK activation is entirely TLR7-dependent. We further demonstrate that NK activation is indirectly induced through IL-12 and type I IFN production by dendritic cells. Reconstitution of TLR7-deficient mice with wild-type dendritic cells restores NK activation upon treatment with immunostimulatory RNA oligonucleotides. Thus, by activating both NK cells and CTLs, RNA oligonucleotides stimulate two major cellular effectors of antitumor immunity. This dual activation may enhance the efficacy of immunotherapeutic strategies against cancer by preventing the development of tumor immune escape variants.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0022-1767
e-ISSN
1550-6606
Journal
Journal of Immunology
Quellenangaben
Volume: 183,
Issue: 10,
Pages: 6078-6086
Publisher
American Association of Immunologists
Publishing Place
Bethesda
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)